Lizhi Liu

Cell membrane coated nanoparticles (NPs) have recently been recognized as attractive nanomedical tools because of their unique properties such as immune escape, long blood circulation time, specific molecular recognition and cell targeting. However, the integrity of the cell membrane coating on NPs, a key metrics related to the quality of these biomimetic-systems and their resulting biomedical function, has remained largely unexplored. Here, we report a fluorescence quenching assay to probe the integrity of cell membrane coating. In contradiction to the common assumption of perfect coating, we uncover that up to 90% of the biomimetic NPs are only partially coated. Using in vitro homologous targeting studies, we demonstrate that partially coated NPs could still be internalized by the target cells. By combining molecular simulations with experimental analysis, we further identify an endocytic entry mechanism for these NPs. We unravel that NPs with a high coating degree (≥50%) enter the cells individually, whereas the NPs with a low coating degree (<50%) need to aggregate together before internalization. This quantitative method and the fundamental understanding of how cell membrane coated NPs enter the cells will enhance the rational designing of biomimetic nanosystems and pave the way for more effective cancer nanomedicine.

This paper estimates the impact of the first nationwide e-commerce expansion program on rural households. To do so, we combine a randomized control trial with new survey and administrative microdata. In contrast to existing case studies, we find little evidence for income gains to rural producers and workers. Instead, the gains are driven by a reduction in cost of living for a minority of rural households that tend to be younger, richer, and in more remote markets. These effects are mainly due to overcoming logistical barriers to e-commerce rather than additional investments to adapt e-commerce to the rural population. (JEL I31, L81, O12, O18, P25, P36)

Cell membrane (CM) coating technology is increasingly being applied in nanomedicine, but the entire coating procedure including adsorption, rupture, and fusion is not completely understood. Previously, we showed that the majority of biomimetic nanoparticles (NPs) were only partially coated, but the mechanism underlying this partial coating remains unclear, which hinders the further improvement of the coating technique. Here, we show that partial coating is an intermediate state due to the adsorption of CM fragments or CM vesicles, the latter of which could eventually be ruptured under external force. Such partial coating is difficult to self-repair to achieve full coating due to the limited membrane fluidity. Building on our understanding of the detailed coating process, we develop a general approach for fixing the partial CM coating: external phospholipid is introduced as a helper to increase CM fluidity, promoting the final fusion of lipid patches. The NPs coated with this approach have a high ratio of full coating (~23%) and exhibit enhanced tumor targeting ability in comparison to the NPs coated traditionally (full coating ratio of ~6%). Our results provide a mechanistic basis for fixing partial CM coating towards enhancing tumor accumulation.

Numerous infectious diseases that cause clinical failures and relapses after antibiotic therapy have been confirmed to be induced by pathogenic intracellular bacteria. The existing therapeutic strategies fail to eliminate intracellular bacteria mainly due to a guard reservoir provided by the cell membrane, which can deactivate antibiotics. Herein, we have reported the design of a pH-responsive metal organic framework (MOF)/antibiotic synergistic system for the targeted highly efficient elimination of intracellular bacteria. The obtained tetracycline (Tet)@ZIF-8@ hyaluronic acid (HA) system (abbreviated to TZH) can be taken up by cells owing to the presence of CD44 receptors on the cell surface via an HA-mediated pathway. Zinc ions and antibiotics, released from TZH under acidic conditions caused by bacteria, have a synergistic antibacterial effect both in vitro and in vivo. The clearance rate of TZH to the intracellular bacteria reached over 98% within the limits of biotoxicity, which indicated that this delivery system can pass the cell membrane "barriers" and restore the efficacy of endangered antibiotics. This synergistic strategy shows potential in optimizing the efficacy-dosage correlation of antibiotics for related infection treatments and constructing versatile controlled release delivery systems for a broad range of applications.